Career Development Aim: To develop into an independent, productive clinical investigator focusing on patient-oriented research in the field of HIV and malaria neuropathogenesis. Career Development Methods: An individualized curriculum with focused training in clinical research methodology, tropical infectious diseases, NeuroAIDS research, and mentor/faculty interactions is proposed. Scientific Background: Malaria, a mosquito-borne parasitic disease, and HIV, a viral infection, are two disparate and deadly diseases that are often brought together by overlapping geographic distributions. Even though these pathogens frequently infect the same host, their combined effects on the brain are virtually uninvestigated. Since macrophages are centrally involved in both malaria and HIV pathogenesis, we hypothesize that both of these pathogens disrupt the cytokine network of brain macrophages, thereby contributing to the progression of HIV-associated neurologic disorders (HAND). Research Aim: To determine the impact of malaria co-infection on HIV-associated neurocognitive impairment (NCI). Research Methods: This study will be conducted in Chennai, India where both malaria and HIV are highly prevalent. Malaria co-infection will be detected using an innovative pooling strategy and a sensitive Polymerase Chain Reaction assay. NCI, measured by comprehensive neuropsychological (NP) testing, will be compared between HIV/malaria co-infected and HIV-monoinfected participants. In addition to measures of pathogen activity, a panel of inflammation-associated biomarkers (IAB) will be measured in blood. Changes in NP performance will be compared to changes in measures of pathogen activity and inflammation in the HIV/malaria co-infected group before and after malaria therapy. Combined, these results will identify, for the first time, the contribution of malaria to HIV-associated NCI and the impact of treating malaria. Significance: These studies will lead to - i) improvement in HIV/AIDS care through detection and treatment of malaria coinfection;ii) demonstrate the adverse effect of HIV/malaria co-infection on the brain;iii) stimulate further research in this field. The negative impact of undiagnosed malaria co-infection may justify PCR-related expenses in routine clinical care of HIV-infected individuals in malaria endemic regions of the world. The knowledge gained from this study will significantly improve the assessment, diagnosis, and hence treatment of HIV and malaria associated neurobehavioral deficits among adults. PUBLIC HEALTH RELEVANCE: The knowledge gained from this study will significantly improve the assessment, diagnosis, and hence treatment of HIV and malaria associated neurobehavioral deficits among adults.